Clinical Trial Seeks Potential ARDS Treatment

MultiStem® Therapy in Acute Respiratory Distress Syndrome shows promising early results

Innovations in Pulmonology and Sleep Medicine - Summer | 2019

For the more than 200,000 patients diagnosed every year with Acute Respiratory Distress Syndrome (ARDS), there are few treatment options. Anywhere from 30 to 50 percent of those diagnosed will die of the disease, according to the American Lung Association. 

Frank Jacono, MD

ARDS is a severe form of lung injury, most frequently caused by sepsis, inhalation injuries, pneumonia or trauma, explains Frank Jacono, MD, Division of Pulmonary, Critical Care and Sleep Medicine, University Hospitals Cleveland Medical Center; Chief, Pulmonary and Critical Care Medicine Section, Louis Stokes Cleveland Veterans Affairs Medical Center; and Associate Professor, Case Western Reserve University School of Medicine. 

“The common final pathway is significant and severe injury to the lungs such that the interface between the alveoli and the vasculature of the lungs is damaged, and fluids and proteins leak out of the capillaries and fill the alveoli with fluid,” Dr. Jacono says. “This causes pulmonary edema and patients develop hypoxemia.”

In the ICU, physicians take steps to minimize further injury from the ventilator by using low tidal volume settings, positive end-expiratory pressure (PEEP), prone positioning and paralytic agents.

“However, these measures do not address the ongoing injury to the lungs,” Dr. Jacono says. “Many patients who survive are left with lung fibrosis and pulmonary impairments for the rest of their lives. There’s a big need in the field for newer, novel ARDS therapies.”

ARDS CLINICAL TRIAL UNDERWAY

To that end, UH is participating in a Phase I/II clinical trial called MultiStem® Therapy in Acute Respiratory Distress Syndrome (MUST-ARDS). In fact, UH is the largest enrolling site in the United States and the United Kingdom.

MultiStem is a bone-marrow cell therapy product derived from multi-potent adult progenitor cells, Dr. Jacono explains. A product of Cleveland-based Athersys Inc., MultiStem has been used in other medical conditions. However, it’s never been investigated for ARDS — until now.

“In the MUST-ARDS trial, MultiStem cells are infused in subjects with severe ARDS,” he explains. “In the lungs, these cells secrete factors to enhance healing, increase tissue repair and decrease destructive inflammation. Since they are not stem cells, they don’t stay in the body, but while in the lungs, they serve an immunomodulation function.”

The key focus of MUST-ARDS is to assess the safety and tolerability for patients and to evaluate secondary outcomes, including longer-term safety and tolerability, effect on pulmonary function and mortality. The study will also evaluate blood biomarkers to assess the feasibility of MultiStem as a treatment option for ARDS.

Thirty-six subjects have been enrolled in MUST-ARDS, a randomized, double-blind, placebo-control study. The first three subjects received a low dose of MultiStem in open label with no placebo control. The next three subjects received a higher dose. None of the initial six subjects had recognized adverse side effects. The final 30 subjects were randomized 2:1 to the investigational product or placebo. All subjects will be evaluated at seven, 28 and 365 days. 

EARLY RESULTS ARE PROMISING

So far, all subjects have completed their 28-day visit, and the initial data suggest that the safety and tolerability are good, Dr. Jacono says. In fact, the 28-day data results were accepted as a late-breaking clinical trial abstract in the May 2019 American Thoracic Society conference.

“Although the sample size is too low to really draw conclusive conclusions, initial biomarker data is supportive of the fact that MultiStem may be having a beneficial effect,” Dr. Jacono says. “We have to wait for all subjects to complete their one-year follow-up and then all the data will be unblinded.

“If the preliminary results hold up, if MultiStem looks well tolerated with signs it is effective, the plan is to go ahead with a larger trial to determine whether we should offer MultiStem more broadly to patients with severe ARDS,” he says.

UH COMMITTED TO FINDING NEW TREATMENTS FOR ARDS

ARDS is associated with significant morbidity and mortality, and there are currently no effective therapies to help patients with the disease. UH is hoping to change this by participating in cutting-edge research, such as the MUST-ARDS study, to help investigate and identify future therapies.

If you have questions about ARDS or the MUST-ARDS clinical trial, contact Dr. Jacono at fjj@case.edu.